Hepatic stellate cells (HpStCs) were first described by Kupffer in the 19th century and were designated as “Sternellen” for their “stellar” sparkle when viewed under a microscope. HpStCs are liver-specific mesenchymal cells found in the Space of Disse and are comprised, in significant part, of cytoplasmic lipid droplets containing vitamin A. In fact, the lipid droplets contribute to the “sparkle” quality associated with HpStCs.
It is now accepted that HpStCs play a major role in the uptake, storage and release of vitamin A compounds, which are necessary particularly for vision, reproduction, and embryonic development. In mammals, about 50 to 80% of the total body vitamin A is normally stored in HpStCs.
HpStCs also play a central role in the production of growth factors, extracellular matrix components (ECMs), and matrix metalloproteinases in liver. A number of reports demonstrate that HpStCs secrete several mitogens for hepatocytes—such as EGF, TGFα and HGF—and play a central role in liver development and regeneration. Similarly, a numbers of studies demonstrate that an imbalance in ECM regulation is a factor in liver fibrosis or cirrhosis. Furthermore, the contractile properties of HpStCs suggest that they have a similar function to the pericytes, which control local blood flow in blood vessels. Taken together, these diverse functions of HpStCs illustrate their significant role in healthy and dysfunctional hepatic function.
Despite our growing understanding of the importance of HpStCs, the origin of HpStCs remains unknown. In early liver development, endodermal cells in the foregut give rise to hepatic diverticulum, which, in turn, develops into surrounding mesoderm called the septum transversum and forming the hepatic cords. While some have presumed that HpStC progenitors could derive from mesenchymal cells in the septum transversum, no HpStCs have been isolated from it, and surface markers enabling immunoselection and/or characterizing precursor HpStCs have yet to be identified.
Accordingly, there is a need for markers that specifically identify precursors to HpStCs and for a method of isolating same with said markers. In addition, there is a need for a method of propagating HpStC precursor cells in vitro.